DOI
https://doi.org/10.25772/2QBJ-EK47
Defense Date
2014
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Mechanical and Nuclear Engineering
First Advisor
Dr. John E. Speich
Second Advisor
Dr. Paul H. Ratz
Third Advisor
Dr. Rebecca Heise
Fourth Advisor
Dr. Charles Cartin
Fifth Advisor
Dr. Woon Hong Yeo
Abstract
Muscle mechanical behavior potentially plays an important role in some of the most common bladder disorders. These include overactive bladder, which can involve involuntary contractions during bladder filling, and impaired contractility or underactive bladder, which may involve weak or incomplete contractions during voiding. Actin-myosin cross-bridges in detrusor smooth muscle (DSM) are responsible for contracting and emptying the bladder. The total tension produced by muscle is the sum of its preload and active tensions. Studies suggest that actin-myosin cross-links are involved in adjustable preload stiffness (APS), which is characterized by a preload tension curve that can be shifted along the length axis as a function of strain history and activation history. DSM also exhibits length adaptation in which the active tension curve can exhibit a similar shift. Actin-myosin cross-bridges are also responsible for myogenic contractions in response to quick stretch of DSM strips and spontaneous rhythmic contractions (SRC) that may occur during bladder filling. Studies show that SRC may participate in the mechanical regulation of both APS and length adaptation. However, the mechanical mechanisms by which actin-myosin interactions enable this interrelated combination of behaviors remain to be determined and were the primary focus of this dissertation. The objectives of this study were to: 1) provide evidence to support the hypothesis that a common mechanism is responsible for SRC and myogenic contraction, 2) develop a sensor-based mechanical model to demonstrate that SRC in one cell is sufficient to trigger stretch-induced myogenic contraction in surrounding cells and propagate the contraction, and 3) develop a conceptual model with actin-myosin cross-bridges and cross-links that produces the coupled mechanical behaviors of APS, SRC, and length adaptation in DSM. Improved understanding of bladder biomechanics may enable the identification of specific targets for the development of new treatments for overactive and underactive bladder.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
12-12-2014
Included in
Biomechanical Engineering Commons, Biomechanics and Biotransport Commons, Molecular, Cellular, and Tissue Engineering Commons, Other Biomedical Engineering and Bioengineering Commons